The purpose of this project is to analyze the hormonal control of calcium metabolism during pregnancy, intra-uterine growth, and postnatal development. In particular these studies focus on the role of the vitamin D-endocrine system. An important role for vitamin D in developmental and reproductive biology is indicated by documented alterations in vitamin D metabolism and tissue responses during pregnancy, lactation, and postnatal development. A role of vitamin D in controlling placental function is suggested by the finding in placenta of a calcium binding protein (CaBP) identical to the vitamin D-dependent CaBP in intestine. This concept is further supported by recent evidence that the placenta contains receptors for 1,25 dihydroxycholecalciferol. Experiments are designed to directly assess whether placenta is a target tissue for vitamin D metabolite action. Using both in vitro placental organ culture and in vivo microinjection techniques into the mouse/rat fetal compartment, we will assess the effects of vitamin D metabolites upon placental function as reflected by induction of CaBP and calcium transport. The subcellular localization of CaBP in placenta will be studied using immunohistological techniques. These observations will advance our understanding of the function of this protein as related to placental calcium transport. The CaBP mRNA of both placenta and intestine will be characterized with respect to its cell-free translation products and vitamin D dependency. These experiments will determine whether mammalian CaBP is synthesized as a precursor as suggested by others. Studies with 1,25(OH)2D will assess whether vitamin D increases the amount of CaBP mRNA as in chickens of affects processing of the putative precursor of CaBP. These experiments will be the first mRNA analyses of mammalian CaBP and therefore will be important for understanding the genetic expression of CaBP in mammalian development. A final set of experiments will assess the role of mRNA accumulation in producing changes in placental and intestinal CaBP content during pregnancy and growth. These studies promise to increase our understanding of physiologic processes of the perinatal period and to provide tools for the study of their pathologic alterations.